Roles of IL-25 in Type 2 Inflammation and Autoimmune Pathogenesis

Deng, Chao; Peng, Na; Tang, Yuan; Yu, Na; Wang, Cuicui; Cai, Xiaoyan; Zhang, Lijun; Hu, Dajun; Ciccia, Francesco; Lü, Lei

doi:10.3389/fimmu.2021.691559

Cited by 40 publications

(31 citation statements)

References 91 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It should be noted, however, that the Conv (Rm2) showed relatively high upregulation of IL-25. It is known that IL-25 can be produced by Th2 cells along with ILC2s, macrophages and other monocytes, which may be a reason for upregulation of this cytokine in these mice ( 84 ).…”

Section: Discussionmentioning

confidence: 99%

Contribution of the Microbiome, Environment, and Genetics to Mucosal Type 2 Immunity and Anaphylaxis in a Murine Food Allergy Model

et al. 2022

View full text Add to dashboard Cite

There is heterogeneity inherent in the immune responses of individual mice in murine models of food allergy, including anaphylaxis, similar to the clinical heterogeneity observed in humans with food allergies to a defined food. One major driver of this heterogeneity may be differences in the microbiome between sensitized individuals. Our laboratory and others have reported that disruption of the microbiome (dysbiosis) by broad spectrum antibiotics and/or yeast colonization can alter systemic immunity and favor the development of mucosal Type 2 immunity to aeroallergens. Our objective was to use a well-characterized murine model (Balb/c mice) of food allergies (chicken egg ovalbumin, OVA) and determine if antibiotic-mediated dysbiosis (including C. albicans colonization) could enhance the manifestation of food allergies. Furthermore, we sought to identify elements of the microbiome and host response that were associated with this heterogeneity in the anaphylactic reaction between individual food allergen-sensitized mice. In our dataset, the intensity of the anaphylactic reactions was most strongly associated with a disrupted microbiome that included colonization by C. albicans, loss of a specific Lachnoclostridium species (tentatively, Lachnoclostridium YL32), development of a highly polarized Type 2 response in the intestinal mucosa and underlying tissue, and activation of mucosal mast cells. Serum levels of allergen-specific IgE were not predictive of the response and a complete absence of a microbiome did not fully recapitulate the response. Conventionalization of germ-free mice resulted in Akkermansia muciniphila outgrowth and a higher degree of heterogeneity in the allergic response. C57BL/6 mice remained resistant even under the same dysbiosis-inducing antibiotic regimens, while changes in the microbiome markedly altered the reactivity of Balb/c mice to OVA, as noted above. Strikingly, we also observed that genetically identical mice from different rooms in our vivarium develop different levels of a Type 2 response, as well as anaphylactic reactions. The intestinal microbiome in these mice also differed between rooms. Thus, our data recapitulate the heterogeneity in anaphylactic reactions, ranging from severe to none, seen in patients that have circulating levels of food allergen-reactive IgE and support the concept that alterations in the microbiome can be one factor underlying this heterogeneity.

show abstract

Section: Discussionmentioning

confidence: 99%

Contribution of the Microbiome, Environment, and Genetics to Mucosal Type 2 Immunity and Anaphylaxis in a Murine Food Allergy Model

et al. 2022

View full text Add to dashboard Cite

show abstract

“…IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) released from damaged epithelium directly activate the production of IL-4, 5, 9, 13, and 31 from ILC2 and Th2 cells, thus characterizing type 2 inflammation immunity ( Akdis, et al, 2020 ). Both IL-25 and IL-33 can activate MAPK and NK-κB signaling pathways via binding to IL-17RA/B and IL-1 receptor-like 1 (IL1RL1), respectively ( Akdis, et al, 2020 ; Deng, et al, 2021 ). By activating signal transducer and activator of transcription (STAT), skin LC/DC-derived and keratinocyte-derived TSLP are critical for Th2-type immune responses and mediating pruritus exacerbation, respectively ( Kim et al, 2013 ).…”

Section: Immunosenescence and Type 2 Inflammatory Dermatosismentioning

confidence: 99%

Skin Immunosenescence and Type 2 Inflammation: A Mini-Review With an Inflammaging Perspective

Chen

Yang

Song

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Skin-resident stromal cells, including keratinocytes, fibroblasts, adipocytes, and immune cells including Langerhans cells, dendritic cells, T cells, and innate lymphoid cells, and their functional products work in concert to ensure the realization of skin barrier immunity. However, aging-induced immunosenescence predisposes the elderly to pruritic dermatoses, including type 2 inflammation-mediated. Inflammaging, characterized by chronic low level of pro-inflammatory cytokines released from senescent cells with the senescence-associated secretory phenotype (SASP), may drive immunosenescence and tangle with type 2 inflammatory dermatoses. The present mini-review summarizes current evidence on immunosenescence and type 2 inflammation in the skin and further focuses on future needs from an inflammaging perspective to clarify their complexity.

show abstract

“…43 TH17 cells predominantly exert their action by producing the IL-17 family of cytokines (IL-17A-17F), of which IL-17A and IL-25 (IL-17E) are thought to play pivotal roles in pulmonary inflammation through IL-17RA-containing heterodimeric receptor complexes expressed in airway smooth muscle cells. 43 In a phase 2a RCT studying the anti-IL-17RA monoclonal antibody brodalumab, which blocks IL-17A, IL-17F, and IL-17E (IL-25), no improvements were observed in the primary end point of ACQ after 12 weeks of treatment in patients with inadequately controlled moderate-to-severe asthma. 44 Any improvements in the secondary end point of FEV 1 also did not amount to statistical significance or a clinically meaningful response.…”

Section: Brodalumab (Anti-il-25)mentioning

confidence: 99%

Targeting Downstream Type 2 Cytokines or Upstream Epithelial Alarmins for Severe Asthma

Chan

Stewart

Misirovs

et al. 2022

The Journal of Allergy and Clinical Immunology: In Practice

View full text Add to dashboard Cite

Roles of IL-25 in Type 2 Inflammation and Autoimmune Pathogenesis

Cited by 40 publications

References 91 publications

Contribution of the Microbiome, Environment, and Genetics to Mucosal Type 2 Immunity and Anaphylaxis in a Murine Food Allergy Model

Contribution of the Microbiome, Environment, and Genetics to Mucosal Type 2 Immunity and Anaphylaxis in a Murine Food Allergy Model

Skin Immunosenescence and Type 2 Inflammation: A Mini-Review With an Inflammaging Perspective

Targeting Downstream Type 2 Cytokines or Upstream Epithelial Alarmins for Severe Asthma

Contact Info

Product

Resources

About